impact of comorbidity on cognitive-behavioral therapy...

Impact of Comorbidity on Cognitive-BehavioralTherapy Response in PediatricObsessive-Compulsive Disorder

ERIC A. STORCH, PH.D., LISA J. MERLO, PH.D., MICHAEL J. LARSON, M.S.,GARY R. GEFFKEN, PH.D., HEATHER D. LEHMKUHL, PH.D., MARNI L. JACOB, B.S.,

TANYA K MURPHY, M.D., AND WAYNE K. COODMAN, M.D.

ABSTRACT

Objective: To examine the impact of psychiatric comorbidity on cognitive-behavioral therapy response in children andadolescents with obsessive-compulsive disorder. Method: Ninety-six youths with obsessive-compulsive disorder (range7-19 years) received 14 sessions of weekly or intensive family-based cognitive-behavioral therapy. Assessments wereconducted before and after treatment. Primary outcomes included scores on the Children's Yale-Brown Obsessive-Compulsive Scale, response rates, and remission status. Results: Seventy-four percent of participants met criteria for atleast one comorbid diagnosis. In general, participants with one or more comorbid diagnoses had lower treatment responseand remission rates relative to those without a comorbid diagnosis. The number of comorbid conditions was negativelyrelated to outcome. The presence of attention-deficit/hyperactivity disorder and disruptive behavior disorders was relatedto lower treatment response rates, and the presence of disruptive behavior disorders and major depressive disorder wererelated to lower remission rates. Conclusions: The presence of a comorbid disorder, particularly disruptive behavior,major depressive, and attention-deficit/hyperactivity disorders, has a negative impact on treatment response. Assessingfor psychiatric disorders before treatment entry and treating these comorbid conditions before or during cognitive-behavioral therapy may improve final outcome. Comorbid anxiety or tic disorders do not seem to negatively affectresponse. J. Am. Acad. Child Adolesc. Psychiatry, 2008;47(5):583-592. Key Words: obsessive-compulsive disorder,cognitive-behavioral therapy, comorbidity, children, treatment. Clinical trials registration information-URL: http://clinicaltrials.gov. Unique identifier: NCT00369642.

Obsessive-compulsive disorder (OCD) among childrenand adolescents is a debilitating and chronic psychiatriccondition' with prevalence rates ranging from 1% to4%."3 Comorbid conditions such as depression,anxiety, disruptive behavior disorders (DBDs), andattention-deficit/hyperactivity disorder (ADHD), tendto be the rule rather than exception in pediatric

Accepted September 13, 2007.Drs. Storch, Merlo, Geffken, Lehmkuhb Murphy, and Goodman andMs.Jacob

are with the Department of Pychiatry, and Mr. Larson is with the Departmentof Clinical and Health .Psychology, Universiy offFlonrida.

This article is the subject of an editorial by Dr. John Piacentini in this issue.Correspondence to Dr. EricA. Storch, Department ofPsychiatry, University of

Florida, Box 100234, Gainesville, FL 32610; e-mail: [email protected]/4705-0583@2008 by the American Academy of Child and

Adolescent Psychiatry.DOI: 10.1097/CHI.0b013e31816774bi

J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 47:5, MAY 2008

OCD,"-7 often affecting functional impairment aboveand beyond the OCD diagnosis. 8-12

Two treatment modalities have demonstrated efficacyin pediatric OCD patients, namely, pharmacotherapywith serotonin reuptake inhibitors (SRI) and cognitive-behavioral therapy (CBT) with exposure and responseprevention. 13 Pooled effects suggest that CBT may havesome advantage over SRI treatment alone, 14 leading tothe suggestion that children receive CBT alone ortogether with SRI therapy. 15 However, despite the factthat CBT is an effective intervention with someadvantages over medications in terms of efficacy,durability after treatment withdrawal,16 and safety, notall youths respond to CBT and some are unable orunwilling to participate.

Clinical experience and limited data suggest that onefactor that influences CBT outcome is psychiatric

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comorbidity. However, the results of previous researchhave produced somewhat mixed findings. Amongadults, several studies found that severely depressedOCD patients responded less frequently than those whowere not severely depressed'7-20 (see Orloff et al. 2 1 foran exception). Among children, March et al 2 2 foundthat the presence of a tic disorder did not affect CBToutcome but negatively affected response to sertraline.Himle et al. 23 also found that the presence of acomorbid tic disorder did not affect CBT response.Storch et al.2 4 found that anxiety comorbidity did notaffect CBT response in a sample of38 youths. However,the number of comorbid conditions in general wasinversely related to outcome, such that those youthswith more than one comorbidity exhibited worseresponse.

Additional evidence of the impact of comorbidity ontreatment response is derived from pharmacologicaltrials and studies of CBT in other psychiatric conditions.Most notably, Geller et al.25 examined the influence ofcomotbidity on treatment response in 193 youthstreated with paroxetine. In contrast to the overall sampleand those without any comorbidity (71% and 75% wereresponders, respectively), youths with ADHD, tics, andoppositional defiant disorder (ODD) exhibited signifi-cantly worse response (56%, 53%, and 39%, respec-tively). Others have also shown that the presence of acomorbid tic disorder negatively affects pharmacother-apy response 22,26,27 (see March et al. 28 for an excep-tion). In CBT studies with other pediatric psychiatricpopulations, ADHD, anxiety, and DBDs have nega-tively affected CBT response in depression. 2930 It isunclear whether comorbidity affects CBT outcome inchildren with an anxiety disorder. Three studies31- 3

have found that CBT response was not affected by thepresence of comorbid internalizing or externalizingbehaviors. Berman et al.,3 4 however, found thatcomorbid depression, but not disruptive behavior,negatively affected CBT outcome.

Despite these data, little information is availableregarding the effect of varied comorbidities on CBTresponse in pediatric OCD. The authors' clinicalexperience, together with the limited literature reviewedabove, suggests the following diagnoses, in particular,may negatively affect outcome: depressive disorders,DBDs, and ADHD. Theoretically, comorbid condi-tions may affect CBT response by forcing the clinicianto focus on both the primary and comorbid conditions,

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thus reducing the amount of time spent duringtreatment on OCD-related tasks. The presence ofdepressive disorders may be associated with decreasedanxiety habituation during exposures, 35 as well asdecreased hope that treatment may work or motiva-tion/energy to engage in exposures. The presence ofDBDs is often linked to patient resistance to engage inexposures and increased secondary gains from symptoms(i.e., missing school, decreased role expectations), whichserve to maintain the OCD symptoms. Finally, thepresence of ADHD may be associated with decreasedability to attend to concepts discussed within therapy,3 3

as well as deficits in executive functioning necessary toindependently plan and implement exposures and othertherapeutic tasks (e.g., engage in thought challenging).3 6

The possible impact of comorbidity on CBT responsehas significant clinical implications for assessment andtreatment planning. For example, if the presence ofcomorbid depression and/or ADHD is associated withattenuated response, pharmacotherapy may be bene-ficial before initiating CBT. Similarly, parent manage-ment training programs3 7 that teach parents adaptivechild management skills may be warranted beforeconducting CBT. With this in mind, we had twogoals. First, we sought to examine the influence of thepatients' number of comorbid diagnoses on responseand remission rates. Based on work by Storch et al.2 4

and Geller et al.,25 we expected that the number ofcomorbid conditions present would be negativelyassociated with outcome. Second, we were interestedin studying the impact of a range of comorbid illnesseson CBT response and remission rates. Based on theabove data and our clinical experiences, we expected thatthe presence of depressive disorders, DBDs, and ADHDwould be negatively associated with CBT outcome.

METHOD

ParticipantsNinety-six children and adolescents (43 female, 45%) ranging in

age from 7 to 19 years (mean 13.5 ± 3.3 years) participated in thisstudy. All of the participants had a principal diagnosis of OCD,according to DSM-1V-TR criteria, made by a clinical childpsychologist or board-certified child and adolescent psychiatrist,based on clinical interview. Diagnoses were established through aclinical interview with the first or second author and administrationof the Anxiety Disorders Interview Schedule for DSM-IV- ParentVersion (ADIS-IV-P) 38 and Children's Yale-Brown ObsessiveCompulsive Scale (CY-BOCS)39 by a separate trained evaluator.All of the diagnoses were then confirmed by a board-certified child


PEDIATRIC OCD

and adolescent psychiatrist or licensed clinical psychologist after areview of all of the clinical information, as well as results fromcollateral assessment instruments (e.g., Children's DepressionInventory). Disagreements were resolved via a discussion of relevantclinical data. In the infrequent instance that this did not resolve thedebate, the interviewing clinician made the final decision (althoughit should be noted that this never occurred for the primarydiagnosis). In the case of tic disorders (Tourette's syndrome orchronic tic disorder), which the ADIS-IV-P does not assess, DSM-IVdiagnoses were derived exclusively from clinical interview andadministration of the Yale Global Tic Severity Scale.40 Only subjectsfor whom all of the clinicians agreed on primary diagnostic statuswere included in the study (100% interrater agreement). Baselinedemographic and clinical characteristics are included in Table 1.

Participants were recruited from both the normal patient flow atthe University of Florida OCD Program, as well as those whoparticipated in a clinical trial examining differential efficacy betweenintensive and weekly CBT.41 The impact of any anxiety comorbidityon CBT response for youths enrolled in Storch et al.4' was examinedin a separate report.2 4 However, the use of the clinic sample in thisstudy more than doubles the sample of Storch et al.24 and allows forthe use of multiple different outcomes and specific examination ofthe effects of individual disorders, which was not possible in theStorch er al.24 study. Regardless of their point of entry, all of theparticipants completed human subjects informed consent processesapproved by the University of Florida Institutional Review Board.Inclusion criteria were principal diagnosis of OCD made based onthe ADIS-IV-P and CY-BOCS Total Score _>16; no change inpsychotropic medication (if applicable) for at least 8 weeks beforestudy entry; and availability of a parent to attend all of the sessions.Exclusion criteria were history of and/or current psychosis, autism,

TABLE 1Baseline Clinical Characteristics of OCD Patients With and Without

Comorbid DiagnosesOCD OCD + Comorbidity t or

Source (n = 25) (n = 71) X2 p

Sex (male), no. (%) 13 (52) 40 (56) 0.14 .71Age, y 13.94 (3.07) 13.40 (3.43) 0.69 .49Ethnicity (white), 24 (96) 67 (94) 1.66 .44

no. (%)Annual family $83,428 $85,716 ($48,047) 0.21 .84

income ($25,842)ADIS-IV-P 5.99 (1.28) 5.84 (1.25) 0.49 .62

Severity IndexCY-BOCS 23.40 (6.33) 28.75 (5.01) 4.27 .001

Total ScoreCY-BOCS 11.56 (3.37) 14.15 (3.05) 3.56 .001

ObsessionsCY-BOCS 11.84 (3.64) 14.53 (2.57) 4.03 .001

CompulsionsCGI-S 3.48 (.87) 4.11 (.95) 2.93 .004

Note: Data include mean (SD) unless otherwise specified. OCD =obsessive-compulsive disorder; ADIS-IV-P = Anxiety DisordersInterview Schedule for DSM-IV: Parent Version; CY-BOCS =Children's Yale-Brown Obsessive-Compulsive Scale; CGI-S =Clinical Global Impressions-Severity scale.


bipolar disorder, substance use, or current suicidality measured bythe ADIS-IV-P and all of the available clinical information and apositive diagnosis in the caregiver of mental retardation, psychosis, orother psychiatric disorders or conditions that would limit his or herability to understand CBT (based on clinical interview). Themajority of youths (n = 68) were receiving medication for OCD atthe time of the study. To be considered a clinically effective SRI dose(i.e., clomipramine, citalopram, escitalopram, fluoxetine, fluvox-amine, paroxetine, and sertraline), subjects had to be taking theirmedication for at least 12 weeks or be unable to tolerate themaximum dose due to side effects (based on parent report). Aminimum adequate SRI dose was defined as the mean effective SRIdose established in double-blind trials in pediatric OCD patients orin pediatric depression when OCD data were not available. Of thesample, 38 were receiving an SRI medication alone, six were takingtwo or more SRIs, and 24 were taking an SRI together with anatypical antipsychotic medication. Four youths taking an SRImedication alone were taking a suboptimal dose with no knownreason why doses were not titrated upward. Sixteen youths weretaking a stimulant in addition to their other psychotropicmedication(s), and two youths were taking a stimulant medicationalone. All of the psychotropic medications remained stablethroughout the duration of the study.

Measures

ADIS-IV-P. The ADIS-IV-P38 is a clinician-administered,structured interview that assesses for the presence and severity ofDSM-IV anxiety and related disorders (i.e., DBDs, depressivedisorders, ADHD). Diagnoses are made as a function of symptomendorsement with an associated distress/impairment severity ratingof Ž4 (on a scale of 0-8). The ADIS-IV-P has strong psychometricproperties in assessing both anxiety disorder diagnoses and relatedcomorbid disorders. 42 For example, Silverman et al.42 found goodstability over 7 to 14 days for ADHD and ODD diagnoses (K = 1.0and 0.78, respectively) and Lyneham et al.4 3 found good interrateragreement for ADHD and ODD diagnoses (K = .77 and .73,respectively).CY-BOCS. The CY-BOCS3 9 is a 10-item, clinician-rated measure

of OCD severity. Items assess the frequency, impairment, distress,resistance, and control associated with obsessions and compulsions.The following scores were calculated: an Obsession Severity score(five items), Compulsion Severity score (five items), and Total Score(sum of all items). Considered the gold standard in pediatric OCDsymptom severity assessment, the CY-BOCS has sound reliabilityand construct validity properties39,44 as well as treatmentsensitivity.15Clinical Global Impressions-Improvement (CGI-I) Scale. The CGI-I

scale 45 is a widely used clinician-rated measure of treatmentresponse. Ratings of treatment outcome on this 7-point scale rangefrom 1 (very much improved) to 7 (very much worse). Ratings ofvery much improved or much improved were defined a priori astreatment responders.

Procedures

Assessments. Assessments were conducted immediately beforebeginning treatment (either 14 weekly sessions or 14 sessions in 3weeks) and 1 to 3 days after treatment completion. Clinicalpsychology doctoral candidates who were trained in measurementadministration by the first author conducted assessments. Trainingincluded attending an instructional meeting led by the first author,

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observing three administrations of study measures, administeringclinician-rated measures three times with in vivo observation andsupervision. Interrater reliability for the CY-BOCS in a subsample of20 participants was excellent (ic = .96). Interrater reliability was notcollected on the ADIS-IV-P. However, all of the diagnoses generatedby the ADIS-IV-P were reviewed by the first author and confirmedby the fourth or seventh authors. Others43 have found high interraterreliability (ic = .91) for parental endorsements of an OCD diagnosisin their child. Interrater reliability for other disorders assessed by theADIS-IV-P ranging from 0.82 to 0.96 for the principal diagnosis and0.78 to 0.96 for other diagnoses being included in the overalldiagnostic profile.43

At each assessment, assessors administered the ADIS-IV-P andCY-BOCS to parents and children jointly. Per Scahill er al. 9 CY-BOCS ratings were based on both parent and child responses, as wellas clinician judgment and behavioral observation. After thecollection of all of the information (e.g., ADIS-IV-P, CY-BOCS,unstructured clinical interview), the first or second author confirmeddiagnoses with a licensed psychologist otherwise not involved inparticipants' treatment.

CBT. Participants received individually tailored weekly orintensive family-based CBT. For 40 youths, the treatment formatwas based on their participation in a randomized trial ofweekly andintensive CBT 41; for the others, the choice of intensive or weeklytreatment was based on clinical appropriateness. No difference inoverall efficacy was found between intensive or weekly conditions;thus, groups were combined. The first author assigned a treatmentfidelity rating that has been used by others4 6 (0 = poor fidelity, 5 =excellent fidelity) based on a comparison to the treatment manual.No differences existed in treatment fidelity between those whoparticipated in the CBT trial41 (mean 4.67, SD 0.52. range 3-5)relative to those treated through the normal clinical flow (mean4.67, SD 0.51, range 3-5). Based on the Pediatric Obsessive-Compulsive Disorder Treatment Study15 treatment protocol,psychotherapy for those in the clinical trial4 ' and those recruitedas part of normal clinical care consisted of 14 individual 90-minuteCBT sessions in either a weekly (once per week) or intensive (14sessions over 3 weeks) format. As described in Storch et al., 41sessions were family oriented, with at least one parent participatingin all of the sessions. Sessions I to 3 were devoted topsychoeducation, treatment discussion, and hierarchy develop-ment, and sessions 4 to 14 involved graduated exposure andresponse prevention exercises (both imaginal and in vivo) specific toeach youth. Early exposures were to moderately distressingsituations with progression toward more anxiety-provoking ones.Homework was assigned after each session that consisted ofexposures similar to those focused on in session (Ž60 minutesdaily). The nature of treatment did not differ as a function of theirpoint of entry (e.g., study versus standard clinical care).

Data AnalysesAll of the statistical procedures were performed using SPSS 14.0.

Given that only seven of 96 participants dropped out of treatmentand the primary reason for dropout was lack of improvement, weused last observation carried forward analyses to account for missingdata at the posttreatment assessment. Initial analyses examineddescriptive information for pediatric OCD patients with andwithout comorbid diagnoses. Independent samples t tests wereperformed on continuous variables, and Pearson's X2 analyses wereperformed on categorical variables. Chi-square analysis was used tocompare treatment response in patients with and without comorbid

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diagnoses; the Fisher exact test was used to examine treatmentresponse as a function of specific comorbid conditions. Treatmentresponse was defined a priori as a CGI-I scale score of very muchimproved or much improved and a decrease in the CY-BOCS score>30%. Studies of CBT typically use the stringent criterion of a 50%decrease, which fails to capture meaningful change in some patientswho do not meet this threshold. In acute medication trials,definitions of response have generally included a 25% or 35%decrease in Y-BOCS/CY-BOCS scores from baseline. However, the25% cutoff has resulted in a high number of false positives,47whereas higher cutoff scores resulted in a high number of falsenegatives. Through signal detection analyses, Tolin et al.48

determined that a Y-BOCS decrease criterion of 30% was optimalfor determining clinical improvement and corresponded to clinicallymeaningful improvement. Pearson's correlations were used toexamine the number of comorbid conditions and two measures oftreatment response, percentage of change on the CY-BOCS and theCGI-Improvement scale. Given the preliminary nature of this work,no statistical correction was used for type I error.

Remission was classified as having a severity rating on the ADIS-IV-P <_3 and CY-BOCS Total Score:510. Consistent with analysesof treatment response variables, j2 analysis was used to compareremission rates in patients with and without comorbid diagnoses aswell as to compare remission rates as a function of currentmedication status (no medication, single SRI, or SRI plus anaugmenting agent, either another SRI or an antipsychotic medica-tion). The Fisher exact test was used to examine remission rate as afunction of each specific comorbid condition. Patients only takingstimulant medication for ADHD and no medication for OCD wereexcluded from analyses of the impact of medication on treatmentresponse. It is worth noting that response and remission ratesrepresent separate but related constructs that may be differentiallyaffected across comorbid conditions.

RESULTS

Preliminary AnalysesOf the 96 patients enrolled, 71 (74%) met criteria for

a comorbid psychiatric disorder. Comorbid diagnosesincluded generalized anxiety disorder (n 32; 33%),major depressive disorder (MDD; n = 25; 26%),ADHD (n = 25; 26%), DBDs (includes ODD, conductdisorder, and DBD not otherwise specified: n = 21;22%), social phobia (n = 15; 16%), Tourette syndromeand chronic tic disorder (n = 9; 9%), panic disorder (n =7; 7%), and Asperger syndrome (n = 2; 2%). Given itslow frequency, Asperger syndrome was not included inanalyses of individual comorbidities. Descriptive clinicaland demographic information for the OCD and OCDplus comorbid diagnosis groups is presented in Table 1.Groups did not differ on the demographic variables ofage, sex ratio, ethnicity ratio, or average yearly familyincome. Comorbidity groups differed on all measures ofbaseline OCD severity, with OCD patients withcomorbid diagnoses exhibiting more severe OCDsymptoms.


PEDIATRIC OCD

TABLE 2Posttreatment Clinical Characteristics and Treatment Response

of OCD Patients With and Without Comorbid DiagnosesOCD OCD + Comorbidity

Source (n = 25) (n = 71) t p

ADIS-IV-P 0.92 (0.91) 2.97 (2.17) 6.48 .001SeverityIndex

CY-BOCS 5.92 (4.42) 13.89 (9.40) 4.07 .001Total Score

CY-BOCS 74 (20) 51 (32) 3.31 .001Percentageof Change

CY-BOCS 3.24 (2.33) 7.32 (4.61) 4.23 .001Obsessions

CY-BOCS 2.68 (2.63) 6.56 (5.16) 3.60 .001Compulsions

CGI-S 1.16 (0.75) 2.21 (1.36) 3.66 .001CGI-I 1.32 (0.63) 2.04 (114) 3.00 .003

Note: Data include mean (SD) unless otherwise specified. OCD =obsessive-compulsive disorder; ADIS-IV-P = Anxiety DisordersInterview Schedule for DSM-IV.: Parent Version; CY-BOCS =Children's Yale-Brown Obsessive-Compulsive Scale; CGI-S =Clinical Global Impressions-Severity scale; CGI-I = Clinical GlobalImpressions-Improvement scale.

CBT Response

Treatment Response by Comorbidity. Collapsed acrosscomorbidity groups, 72 of 96 patients (75%) wereconsidered treatment responders with a mean (SD)decrease of 19.60 (5.81) points on the CY-BOCS TotalScore for the treatment responders and 3.38 (4.76) forthe youths not considered treatment responders.Twenty-three of 25 (92%) patients with no comorbiddiagnoses were considered treatment responders, whichrepresented a significantly greater percentage than the49 of 71 (69%) of patients with one or more comorbiddiagnoses who were considered treatment responders(X2 1 = 5.21; p < .02). Treatment response for patientswho met criteria for two or more (31 of 46; 67%) orthree or more comorbid psychiatric disorders (13 of 20;65%) did not significantly differ from those with one ormore comorbid disorder (X2 < 1.35; p >.25), but wassignificantly decreased relative to those with nocomorbid disorders (X2 > 5.06; p < .02). Pearson'scorrelation analysis (two-tailed) indicated that the morecomorbid diagnoses that a patient met criteria for, thelower his or her CY-BOCS percentage of decrease (r(95)= -0.27; p < .008) and CGI-Improvement scale score(r(95) = 0.2 6 ;,p < .01) were after treatment. We should


note that comorbidity groups were not mutuallyexclusive. Thus, the patient group with one or morecomorbid conditions subsumes the patient group withtwo or more comorbid conditions and so on.

Posttreatment means for OCD severity and improve-ment, t values, and significance levels as a function ofcomorbidity group are included in Table 2. Groupsdiffered significantly on all posttreatment measures ofOCD severity, including the ADIS-IV-P Severity Index,CY-BOCS Total Score and, most important, CY-BOCSTotal Score percentage of decrease. Patients in the OCDplus comorbidity group showed significantly higher CY-BOCS Total Scores and lower percentage of changesthan the no comorbidity group.

Treatment Response by Comorbid Condition. Relativeto those without a comorbid disorder, response rateswere significantly lower for patients with comorbidADHD (60%; p < .04) and DBDs (57%; p < .03)(Fig. 1). The ratio of treatment response rates did notsignificantly differ (all p > .50) between patients withand without a comorbid diagnosis of generalized anxietydisorder (72%), MDD (73%), social phobia (66%),Tourette syndrome (66%), or panic disorder (71%).Response rates did not differ between youths withcomorbid ADHD who were and were not on ADHD-focused medication (X2 0.24, not significant).

OCD Remission Rates

Remission by Comorbidity. Remission rates as a functionof comorbid condition are presented in Figure 2. Intotal, 58% of patients (56 of 96) did not meet criteria forOCD after treatment. Ninety-two percent (23 of 25) ofpatients with no comorbid conditions met criteria forremission compared to 46% (33 of 71) of those with atleast one comorbid condition. Consistent with treatmentresponse rates, patients who met criteria for two or more(21 of 46; 45%), or three or more comorbid psychiatricdisorders (7 of 20; 35%) showed decreased remission ratesrelative to those with no comorbid disorders (X2 > 5.84;p <.02), but did not significantly differ from those with one ormore comorbid disorders (x2 < 1.62; p> .20).

Remission by Comorbid Condition. Consistent withtreatment response rates, remission rates were signifi-cantly lower for patients who met criteria for comorbidDBDs relative to those without a comorbid diagnosis(24%; p < .001). In contrast to response rates, remissionrates in participants with comorbid MDD were also

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E All Patients

7 E3* [ No Comorbid Diagnosisc 70.--13 1 or More Comorbidity

CD OADHD75 50, re OGAD

S40 1/MDD0U) CODDa)30-

3 3Panic D/O20o ESocial Phobia10 0 Tourette's10

Diagnosis *p < 0.05

Fig. 1 Treatment response rates (percentage) for patients with obsessive-compulsive disorder as a function ofcomorbid psychiatric disorder. ADHD = attention-deficit/hyperactivity disorder; GAD = generalized anxiety disorder, MDD = major depressive disorder; ODD = oppositional defiant disorder; Panic D/O = panicdisorder; Tourette's = Tourette syndrome.

significantly lower than those without a comorbidcondition (42%; p < .05), whereas participants withcomorbid ADHD did not significantly differ on thisvariable from those without a comorbidity (44%,p > .09). Interestingly, those youths with comorbidADHD not taking an ADHD-focused medication had ahigher remission rate than those taking relevantmedication (X21 = 5.31; P = .02). Relative to thosewithout a comorbid condition, remission rates did notsignificantly differ for patients with comorbid general-ized anxiety disorder (47%; p > .11), social phobia

(40%; P > .12), Tourette syndrome (55%; p > .90), orpanic disorder (43%; p > .39).

Impact of Concomitant Medication

Response and Remission Rates by Medication Status.Twenty-two of 26 patients (85%) taking no medicationduring CBT were treatment responders. This responserate was not significantly different from the 29 of 38(76%) patients taking a single SRI (X2 1 = 3 .2 2 ;p = .073)and the 19 of 30 (63%) patients taking an SRI

CEl No Cororbid Diagnosis2 700 1 or More Comorbiditya)

S60-• • [OADHD50 -

r.0 40- 1- MDD• • 3 ODDE 30-

30 Panic D/O

20" _ Social PhobiaElTourette's

10-0,

Diagnosis P < 0.05Fig. 2 Symptom remission rates for patients with obsessive-compulsive disorder (OCD; percentage who met criteria for remission of OCD symptoms) as afunction of comorbid psychiatric disorder. ADHD = attention-deficir/hyperactivity disorder; GAD = generalized anxiety disorder; MDD = major depressivedisorder; ODD = oppositional defiant disorder; Panic D/O = panic disorder; Tourette's = Tourerre syndrome.

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PEDIATRIC OCD

augmented by either another SRI or an antipsychoticmedication (X21 = 0.66; p = .42). The proportion ofpatients who responded to treatment did not differbetween those taking a single SRI and those takingan SRI augmented by an additional medication(X21 = 1.36; p = .24).

Symptom remission rate for those not taking anymedication was 73% (19 of 26 patients). This remissionrate was not significantly greater than the 23 of 38(61%) patients taking only one SRI (X2 1 = 1.08;p = .30), but was significantly greater than the 13 of 30(43%) patients taking an SRI and an augmenting agent(X2 I = 5.0 3;P = .03). Remission rates for those taking asingle SRI did not differ from those taking an SRIaugmented with an additional medication (X2 1 = 1.99;p = .16).

Medication Status by Comorbidity. A significantlygreater proportion of patients with a comorbid diagnosiswere treated with medication (55 of 69; 80%) than thosewithout comorbid diagnosis (14 of 25; 56%) (X21 =5.28;- = .02). When examining only those patients witha comorbid condition as a function of concomitantmedication group (no medication, single SRI, or SRIplus an augmenting agent), no group differences wereseen in the proportion of treatment responders (X2 < .58;p > .74) or the proportion of patients whose OCDsymptoms remitted (X2 < 1.57; P > .45). Similarly,medication groups did not differ in treatment response(x2 < 3.59; p > .17) or proportion with symptomremission (X2 < 2.76; p > .25) when only data frompatients without comorbid conditions were analyzed.

DISCUSSION

CBT is a first-line treatment for pediatric OCD, yetfew data exist on how comorbidity may affect response.Although others have investigated the impact of a rangeof comorbid disorders on CBT outcome in adults withOCD, only the relationship between comorbid tic statusand anxiety and CBT response has been reported inpediatric samples. Consistent with previous research, thepresence of a comorbid disorder among patients in oursample was high, with 74% of our sample having at leastone comorbidity. Comorbid illnesses present in at least20% of the sample included generalized anxietydisorder, MDD, ADHD, and DBDs. Consistent withothers,4' 9-11 rates of symptom severity were higher inthose with a comorbid condition relative to those


without. As noted by Geller et al.,2 5 many pharmaco-logical studies in pediatric OCD have strict criteriaresulting in the exclusion of patients with comorbidities;thus, given that our findings suggest that the clearmajority of patients have at least one comorbidcondition, the generalizability of these studies tonaturalistic clinical samples may be limited.

Consistent with our expectations and the limitedavailable data, the presence of a comorbid disordernegatively affected treatment response. Overall, it isworth noting that the level of symptom decrease seen inthis study is above what is typically seen in SRImonotherapy trials. 25 Almost all of the patients (92%)without a comorbid diagnosis were treatment respon-ders and achieved clinical remission of symptoms. Incontrast, of those with one or more comorbid diagnoses,only 69% met criteria for treatment response and only46% met remission criteria. One way to understand thisfinding is that in patients without a comorbid condition,clinicians are able to direct optimal attention to OCDsymptoms rather than concurrently attempting tomanage comorbid symptoms. In other words, themechanism of action may be that the presence of acomorbidity may decrease the amount of time spentduring a CBT session on OCD-related tasks. In light ofthe observed differences in efficacy found between thosewith and without a comorbidity, the question is raisedregarding whether studies with strict exclusionarycriteria may present an artificially high response rate.49

As discussed further below, features of comorbidconditions may uniquely affect the successful imple-mentation of CBT.

With this point in mind, our hypotheses weregenerally confirmed when examining the impact ofspecific disorders on CBT outcome. DBDs, ADHD,and MDD negatively affected response and/or remissionrates. Thematically, each disorder affects the integritywith which CBT is provided, albeit in somewhatdifferent manners. With DBDs, patients are oftenresistant to engage in therapy-related tasks and may beunwilling to relinquish secondary gains. Similarly, theymay present with limited motivation to confront fearedstimuli and increased willingness to defy the therapist'srequests. Depending on the severity of the DBD, moresession time may be spent responding to tantrums andattempting to convince the child to engage in exposuresthan is spent providing psychoeducation or actuallyperforming exposures. The presence of ADHD may be

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associated with decreased ability to stay focused duringthe therapy session33 or attend to the anxiety-producingstimuli. Patients may become restless during exposures,thereby decreasing experience of habituation. ADHDsymptoms may interfere with children's ability to engagein cognitive restructuring exercises, thereby reducing thebenefit of such interventions. In addition, deficits inexecutive fiinctioning associated with ADHD may makeit more difficult for patients to independently plan andimplement exposures and other therapeutic tasks.36Depressive disorders may be associated with decreasedanxiety habituation during exposures,3 5 as well asdiminished hope for a positive treatment response anddecreased motivation to engage in therapy. Childrenwith comorbid depression may also have more difficultyimagining the benefits of getting better and may bemore discouraged by typical challenges and setbacksduring the course of therapy.

Interestingly, we found that youths whose ADHDwas not being treated pharmacologically had higherremission rates. This may be because youths with moresevere symptoms, both ADHD and overall, receiveadditional pharmacological treatment to manage theiroverall clinical presentation. Supporting this andconsistent with adult data suggesting attenuated CBToutcome for those who have an incomplete response totwo or more psychotropic medications targetingOCD,4 6 our results indicate that those patients takingan SRI and an augmenting agent had a lower remissionrate than those not taking medication. Despite beingrecommended as a first-line treatment,15 few youths hadreceived an adequate CBT trial before initial presenta-tion. It is interesting to consider whether those youthson multiple medications would have had a positive CBTresponse if they had received it earlier in their illnesscourse or, alternatively, those youths on multiplemedications represent a refractory subset who havelimited response to available treatments.

Certain comorbid conditions, such as a tic disorder orgeneralized anxiety disorder, did not negatively affectoutcome. March et al.2 2 suggested that skills learned inCBT for OCD may actually generalize to help treat suchrelated conditions. For example, learning adaptive waysto restructure OCD cognitions or confront anxiety-provoking situations may generalize to non-OCDanxiety symptoms. Similarly, response-prevention stra-tegies for rituals in those with non-tic OCD symptomsmay generalize to tic-like OCD symptoms as well.i

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An important consideration when conductingresearch on comorbid diagnoses with any psychiatriccondition is that of the categorical or dimensional natureof comorbid symptoms. We examined comorbidconditions from both a categorical ("Did a patientmeet criteria for a comorbid disorder?") and adimensional ("How many comorbid conditions werepresent?") perspective to demonstrate the relativecontributions of specific comorbid conditions to OCDtreatment response as well as the detrimental effects ofmultiple comorbid conditions on treatment response.Current results indicate both specific categories (DBD,ADHD, and MDD) and increased number of condi-tions detrimentally affect CBT for pediatric OCD. Thismay be due to increased case complexity or, as notedabove, the specific qualities of the comorbid symptoms.Research examining comorbid symptom severity dimen-sionally and the contribution of increased comorbidsymptom severity as a predictor of treatment response isa logical follow-up to the present study.

This study has several limitations. First, raters wereaware that participants were receiving treatment andinterrater reliability data on the CY-BOCS afterassessment were not collected. Similarly, because thesame rater evaluated each participant before and aftertreatment, it was not possible to maintain blinding totreatment type given the differences in the length oftherapy (e.g., 3 versus 14 weeks). On balance, given thepost hoc nature of these analyses, raters were blinded tothe hypotheses in the present study. Second, our samplewas demographically homogeneous (e.g., largely white)and were members of families with a higher income thanthe U.S. median. Third, given the absence of anystatistical correction, the possibility of committing atype I error is increased. Fourth, due to inclusion/exclusion criteria and low rates in our sample, theimpact of several diagnoses was not assessed (e.g.,Asperger syndrome, separation anxiety disorder, bipolardisorder). Fifth, patients with comorbid diagnoses hadhigher CY-BOCS scores at baseline. Thus, analysesof remission rates that used a score of <10 on theCY-BOCS may have been biased toward increasedremission rates in the patients with no comorbidconditions; however, remission rates also includedADIS-IV-P Severity scores, which did not differbetween patients with and without comorbid diagnosesbefore treatment. Sixth, our use of the ADIS-IV-P wasbased on the competency of the research team in the

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PEDIATRIC OCD

administration of this measure, as well as our hope tominimize participant burden. However, the use of morecomprehensive measures such as the Schedule forAffective Disorders and Schizophrenia for School-AgeChildren-Present and Lifetime Version 51 may haveallowed us to assess a wider range of DSM-IVdiagnoses.Seventh, although we were able to analyze response ratesas a function of medication regimen, we did not havecomprehensive information on the number of previousmedication trials that participants had received. There issome evidence that the number of medication trials maybe associated with attenuated CBT outcomes. 46 Finally,given that many subjects participated in a time-limitedtreatment, it is difficult to objectively evaluate whethercomorbid diagnoses changed after CBT participation,and, thus, these data are not considered.

Our findings highlight the importance of comorbid-ity in the assessment and treatment of pediatric OCDpatients. Before treatment, a comprehensive assessmentof comorbid conditions, particularly those uniquelylinked to attenuated response, should be conducted. Inaddition to a clinical interview, quantitative measuresmay be informative in assessing the presence andseverity of comorbid symptoms. In studies of pediatricOCD, it seems reasonable to include a broad range ofcomorbid illnesses, similar to that in the PediatricObsessive-Compulsive Disorder Treatment Study,15 toensure the generalizability of results. Treatment ofcomorbid conditions before CBT may enhance out-come. For example, conducting parent managementtraining for comorbid DBDs may decrease resistance toexposure participation and improve family involvementin treatment. Pharmacotherapy for ADHD maydecrease attention deficits and allow youths to betterattend to and retain concepts discussed in session. Inaddition to pre-CBT pharmacological treatment fordepression, recent data have identified depression-focused CBT as an effective treatment modality.52'53

Therapy for the depressed OCD patient could initiallytarget depressive symptoms either with medication orCBT before addressing OCD symptoms. Future studiesshould examine which depressive symptoms will remitwith OCD treatment and which would benefit frompreliminary treatment before participation in OCD-focused CBT. Studies examining methods of treatingpediatric OCD patients with comorbid conditions areneeded to effectively transport clinic-based interventionsinto the community.


Disclosure: Dr. Storch has received grant support from the Obsessive-Compulsive Foundation and Genentech Incorporated. Dr. Murphy hasreceived grant support from Bristol-Myers Squibb and PediamedPharmaceuticals. The other authors report no conflicts of interest.

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TITLE: Impact of Comorbidity on Cognitive-Behavioral TherapyResponse in Pediatric Obsessive-Compulsive Disorder

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